Ang II Controls the Expression of Mapkap1 by miR-375 and Affects the Function of Islet β Cells

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• The renin-angiotensin system (RAS) plays a role in regulating islet function.
• The precise mechanisms governing RAS regulation of islet function remain incompletely understood.

Purpose of the Study:

• To investigate the role of the islet-specific microRNA-375 (miR-375) in mediating the effects of the RAS on pancreatic islet beta cells.
• To elucidate the molecular pathway involving miR-375 in RAS-induced changes in beta cell function.

Main Methods:

• Utilized insulin-secreting MIN6 cells for in vitro experiments.
• Transfected cells with miR-375 mimics and inhibitors in the presence or absence of angiotensin II (Ang II).
• Assessed cell viability, Akt phosphorylation (Akt-Ser473), and Mapkap1 protein and mRNA expression.

Main Results:

• Ang II treatment reduced cell viability and Akt-Ser levels in MIN6 cells, effects reversed by miR-375 inhibitors.
• miR-375 mimics decreased cell viability and Akt-Ser levels, while miR-375 inhibitors increased them.
• miR-375 negatively regulated Mapkap1 protein expression, independent of mRNA levels, and Mapkap1 inhibition reduced Akt phosphorylation.

Conclusions:

• Angiotensin II exerts its effects on mouse islet beta cells through the miR-375/Mapkap1 axis.
• This regulatory pathway involves the modulation of Akt phosphorylation in beta cells.
• Findings provide a basis for developing miRNA-targeted strategies for islet protection.